The use of stress-bearing materials for bone replacement is well known. A large number of designs have been used to replace missing or diseased portions of the bone structure which are stress-bearing, such as bone shafts, joints, and tooth roots. These designs include artificial shafts, joints, and associated devices intended to mimic the functions of the human skeletal system. The designs can be quite elaborate. See, for example, U.S. Pat. No. 3,820,167 which disclosed a design for an artificial hip joint.
Shafts and other prostheses for use as the stress-bearing portion of the bone replacement are typically constructed of metal or metal alloys. Such metal pins or artificial joints are constructed of suitable inert metals such as titanium, stainless steels, or alloys of metals such as cobalt, chromium and molybdenum. The metallic pin or joint is sometimes provided with an oxide coating in order to prevent corrosion and instability.
It has been observed in the use of such metallic implants that it is frequently necessary to provide a mechanism to fix its position with respect to adjacent bone and prevent it from shifting in place. Attempts have been made to provide this fixation using a cement. USSR patent application 733,665 published May 15, 1980, discloses an implant-fixing cement comprising a mixture of cartilage, collagen (of unspecified origin), and the patient's blood, which is used to secure an implanted pin in place.
Coating a prosthesis with a material ("bioglass") which purportedly encourages bone growth, thus securing the implant with the ingrowth, was disclosed in French Application Publication No 2,383,656, published Oct. 13, 1978. It has also been attempted to use wire mesh surrounding the stress-bearing member of the prosthesis to provide sufficient flexibility to obtain a firm fit, in some cases aided by additional metal strips (e.g., EPO Publication 071,242, published Feb. 9, 1983) In connection with this mesh, a biodegradable, biocompatible material (for example, collagen of unspecified origin) is employed, apparently to prevent damage to the wire mesh during insertion of the implant. The resulting implant is eventually secured by additional bone growth. Indeed, research has consistently shown that prostheses which have porous metal or porous ceramic surfaces are better secured by bony growth into the porous surface.
An attempt has been made to stimulate this bony ingrowth by providing a bone particle coating. U.S. Pat. No. 3,918,100 describes prostheses made of various metals which are coated using RF sputtering with bone particles in a vacuum. In this disclosure, aluminum oxide substrates are coated with a powder made of lye-treated bone chips. The coated prostheses are said to encourage living bone to grow onto the implant, and the coating finally to be absorbed by the surrounding tissue.
None of the foregoing achieves a satisfactory solution. The materials used are often immunogenic and incapable of inducing or stimulating surrounding bone growth at a sufficient rate to prevent damage due to shifting of the prostheses. The present invention provides prostheses which simulate the ingrowth of bone at sufficient rates to obtain a more satisfactory result. cl DISCLOSURE OF THE INVENTION
An implanted stress-bearing prosthesis should be provided with a means to assure permanent attachment of the prosthesis to the remaining portions of the skeletal system; ideally, it should be provided with means which induces the surrounding bone to intrude into the porous surface of the implant, thus fixing the implant in place. The present invention provides an effective prosthesis which induces bone growth at a rate sufficient to provide rapid fixation.
One aspect of the invention is a prosthesis for implantation as a bone replacement (or partial replacement) which comprises a stress-bearing member combined with an effective amount of an osteogenic factor extract (OFE) in a pharmaceutically acceptable carrier.
Another aspect of the invention is a prosthesis for implantation as bone-replacement which comprises a stress-bearing member combined with a substantially pure osteogenically active protein and an effective amount of TGF-beta, combined with a pharmaceutically acceptable carrier.
Another aspect of the invention is a method for permanent fixation of a stress-bearing prosthesis by inducing bony ingrowth into the stress-bearing member by administration of an effective amount of an OFE in a pharmaceutically effective carrier.
Another aspect of the invention is a method for permanent fixation of a stress-bearing prosthesis by inducing bony ingrowth into the stress-bearing member by administration of a substantially pure osteogenically active protein and an effective amount of TGF-beta, combined with a pharmaceutically acceptable carrier.
Another aspect of the invention is a method for repairing bone defects which comprises administering a bone replacement composition comprising a stress-bearing member in combination with an effective amount of an OFE in a pharmaceutically acceptable carrier.
Another aspect of the invention is a method for repairing bone defect which comprises administering a bone replacement composition comprising a stress-bearing member in combination with a substantially pure osteogenically active protein and an effective amount of TGF-beta, combined with a pharmaceutically acceptable carrier.
Another aspect of the invention is a process for preparing a stress-bearing prosthesis of the invention.